Low dose azithromycin may reduce treatment failure after COPD exacerbation


By Michael Woodhead

28 May 2019

A three month course of low-dose azithromycin may protect people hospitalised with a severe acute exacerbation of COPD from recurrent attacks, a European trial suggests.

The macrolide antibiotic may offer a targeted prevention approach for COPD patients by reducing treatment failure and rehospitalisation in the high-risk period following an acute severe exacerbation, according to Belgian researchers.

In a double blind prospective trial involving 301 patients they randomised patients to azithromycin or placebo within 48 hours of being admitted for an exacerbation, in addition to the standard medicine such as corticosteroids.

Patients in the azithromycin arm of the study received 500mg/day for three days while hospitalised, and then 250 mg twice weekly for three months once they left the hospital.

At three months, treatment failure, defined as treatment intensification with medication, step-up in hospital care or readmission for respiratory reasons (SH) occurred in 49% of patients those in the azithromycin group vs. 60% in the placebo arm.

Those receiving the antibiotic spent 24% fewer days in the hospital and 74% fewer days in the ICU than those taking the placebo. Mortality among those in the azithromycin group was half of the placebo group: 2% vs. 4%.

However the primary endpoint of time to treatment failure did not reach statistical significance in differences between groups. Subsequent follow up showed that  the clinical benefits of the azithromycin were no longer evident at six months

Writing in the American Journal of Respiratory and Critical Care Medicine, the study authors noted the benefits of azithromycin  in reducing treatment failure appeared to be greatest in non-smokers, and current smokers gained little benefit.

Lead study author Professor Wim Jannssens, a respiratory physician at KU Leuven and University Hospitals Leuven, said the goal of the study was to assess whether targeting the highest risk patients for a limited period of time, rather than using azithromycin widely as a chronic preventive treatment for COPD exacerbations, was beneficial to patients.

“We wanted to establish a new treatment option for acute exacerbations with hospitalization as current treatments are clearly insufficient,” he said.

“Equally important, we wanted to see whether continuing azithromycin for a relatively short time after leaving the hospital could interrupt the vicious cycle of relapse, even after treatment withdrawal.”

Although the study could not prove statistical significance of its primary endpoint, “a positive message of the trial is that our strategy reduced hospital time, days in the ICU and recurrent exacerbations in the most severe COPD group,” Professor Janssens said.

A larger phase 4 study with hospital readmission as the primary endpoint was necessary before broad implementation of the current study’s findings, he cautioned. Azithromycin treatment would also have to be used judiciously in light of the risks of arrhythmia and antibiotic resistance, he added.

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